Researchers have developed a substance that kills cancer metastases without harming normal cells

A team of researchers from Bar-Ilan succeeded in developing a new anti-cancer agent that attacks the energy production mechanism of cancer metastases and kills them, without harming normal cells

Prof. Uri Nir, from the Faculty of Life Sciences at Bar-Ilan University, and his team managed to reach an important breakthrough in cancer research after developing a synthetic compound that targets the enzyme essential to the energy production system in cancer cells and metastatic cells derived from them. The newly developed substance, known as E260, kills metastatic cancer cells in mice bearing cancerous tumors without harming healthy cells in the animals. The study was recently published in the leading scientific journal Nature Communications.

In a study that received wide attention, the researchers from Bar-Ilan explained that cancer cells detached from the primary tumor, during their dispersion and migration in the patient's body, can survive harsh living conditions, caused by the low availability of basic nutrients such as glucose, for these cells. Metastatic cells can protect against this metabolic deficiency by reprogramming their metabolic system and energy production set-up. Prof. Nir and his team discovered the existence of an enzyme (FerT) in the mitochondria (the organ that creates energy inside the cells) of cancer cells, but this enzyme is not found in the mitochondria of healthy cells. When the researchers impaired the function of the FerT enzyme in cancer cells in the laboratory, the malignant cells found it difficult to produce energy and died. At the same time, the team began to look for the place of expression of the enzyme in different tissues of the body. Finally, the FerT enzyme was identified only in one specific cell - sperm cells.

The sperm cells are the only cells in the male body that perform their functions outside the body. "Like metastatic cells, the sperm cells are unique in that they can produce energy even in difficult and restrictive living conditions. Upon entering the female birth canal, where there is no blood supply for them, they produce and use high amounts of energy to move quickly towards the egg," explained Prof. Nir . "We found that metastatic cancer cells looked for and identified the specific protein FerT, learned how to produce it and harnessed it, to strengthen their mitochondria and produce energy under restrictive and challenging living conditions."

Using advanced chemical and robotic approaches, the team developed a synthetic compound known as E260 that can be administered orally or by injection to animals or patients. When the compound works in metastatic cells in culture or in mice with a metastatic tumor, E260, the substance E260 enters the metastatic cells and then into the mitochondria ("powerhouse") within these cells. In the mitochondria, E260 binds to the FerT enzyme, impairing its activity and subsequently causing a complete collapse of the 'powerhouse' - the mitochondria.

Prof. Nir points out that cancer cells have a high ability to survive and when they recognize the damage to the 'power plant' they begin to activate a recycling process (called autophagy) aimed at breaking down and restoring the mitochondria. The cycle process itself requires a large amount of energy and the continuous energy consumption leads to a severe lack of energy in the treated cells. This energetic and metabolic crisis eventually results in the death of the metastatic cells. "We treated mice with metastatic cancer and the compound cured them, without any negative or toxic effect on the treated animals. We also tested some normal cells and they were not affected," added Prof. Nir.

Now the researchers hope to move to the next stage, which is 'Phase 1' clinical trials, in humans.

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